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AIDS Research Chief Altered Safety Report
Updated: Wednesday, Dec. 15, 2004 - 3:14 PM
By JOHN SOLOMON
Associated Press Writer
WASHINGTON (AP) - The government's chief AIDS researcher removed some negative safety conclusions from a subordinate's report on a U.S.-funded drug experiment, then ordered the research to resume over objections from his staff, memos show.
As justification, Dr. Edmund Tramont, chief of the National Institutes of Health's AIDS Division, cited his four decades of medical experience and argued that Africans with an AIDS crisis deserved some leniency in meeting U.S. safety standards, according to interviews and documents obtained by The Associated Press.
Tramont's staff, including his top deputy, had urged more scrutiny of the Uganda research site to ensure it overcame record-keeping problems, violations of federal patient safety safeguards and other issues. These problems had forced a 15-month halt to the research into using a single dose of nevirapine to prevent African babies from getting AIDS from their mothers.
AP reported Monday that NIH knew about the problems in early 2002 but did not tell the White House before President Bush launched a plan that summer to spread nevirapine throughout Africa.
Now, officials have new concerns the lone dose of nevirapine may cause long-term resistance to AIDS drugs in the hundreds of thousands of African patients who received it, foreclosing future treatment options.
In July 2003, Dr. Jonathan Fishbein, an expert NIH hired to improve agency research practices wrote Tramont: "I am not convinced that the (Ugandan) site is indeed prepared to become active."
Fishbein contended he should be given time to review Uganda's capabilities and safety monitoring before letting the site reopen, or NIH would risk being "toothless" in its new efforts to clean up sloppy research practices. He added that professional safety monitors hired by NIH had reservations about the site.
Tramont dismissed the safety monitors' concerns, saying he didn't believe they fully understood AIDS.
"I am convinced that this site is ready to resume given the limitations of doing research in any resource-poor, underdeveloped country," Tramont wrote July 8, 2003, in response to Fishbein.
"I want this restriction lifted ASAP because this site is now the best in Africa run by black Africans and everyone has worked so hard to get it right as evidenced by the fact that their lab is now certified," he wrote.
NIH officials acknowledge Tramont rewrote the report and overruled his staff on the reopening, but said he did so because he was more experienced and had an "honest difference of opinion" with his safety experts. They noted Tramont had no financial interest in nevirapine and that the troubled study began well before he joined NIH in 2001.
Those who raised objections "were part of a large team of which Dr. Tramont was the head, and it is important that the people involved in that team should express their opinion and there should be discussion," said Dr. H. Clifford Lane, the NIH's No. 2 infectious disease specialist and one of Tramont's bosses. Lane was designated by NIH to speak to AP on Tramont's behalf.
"But at the end of the day, the final responsibility lies with the head of the team, and it is his job to put that together the way he sees it," Lane said.
Lane said an internal NIH review concluded Tramont had not engaged in scientific misconduct. Separately, the National Academy of Sciences continues to investigate whether the Uganda research was valid.
NIH believes it helped save hundreds of thousands of African babies by allowing nevirapine to be used in single doses to block the AIDS virus, Lane said. But he acknowledged the research was imperfect, and NIH now believes nevirapine should no longer be a first choice for newborn protection - if other options exist - because of the newly discovered problems with resistance.
One of the nation's premier AIDS charities said Tuesday it is concerned the controversy over the 2002 study problems will cause African countries to stop using the drug, and called on medical experts to find ways to get better new solutions into the Third World.
"Rather than focus on withdrawing nevirapine from those who urgently need it, the entire world should focus on how we can provide the funding for infrastructure improvements, training, and drug purchase costs so that more and more women will have access to the most effective drug regimens possible," the Elizabeth Glaser Pediatric AIDS Foundations said in response to AP's stories.
Tramont wrote in 2003 e-mails that he reopened the clinics because he didn't want NIH "perceived as bureaucratic but rather thoughtful and reasonable" and that it was important to encourage Africans' fight against AIDS "especially when the president is about to visit them."
Bush visited the continent a few days after Tramont ordered the clinics reopened.
Tramont's actions, however, drew criticism from his top deputy.
"I think we are cutting off our noses to spite our face here," AIDS Division Deputy Director Jonathan Kagan wrote. "... We should not be motivated by political gains and it's dangerous for you, of all people, to be diminishing the value of our monitors." Tramont prevailed.
Five months earlier, Tramont surprised one of his own medical officers, who had written a report summarizing safety concerns uncovered during a second review of the Uganda trial.
Dr. Betsy Smith's report, finished in January 2003, said the Uganda trial suffered from "incomplete or inadequate safety reporting" and records on patients were "of poor quality and below expected standards of clinical research."
She strongly urged NIH not to make sweeping conclusions about nevirapine based on the Uganda research. "Safety conclusions from this trial should be very conservative," she wrote.
Behind the scenes, Tramont asked to see Smith's report before it was submitted to medical authorities, including the Food and Drug Administration. "I need to see the primary data - too much riding on this report," Tramont wrote Jan. 23, 2003.
A few weeks later, the safety report was published and sent to FDA without Smith's concerns and with a new conclusion.
The study "has demonstrated the safety of single dose nevirapine for the prevention of maternal to child transmission," Tramont's version concluded. "Although discrepancies were found in the database and some unreported AEs (adverse reactions) were discovered ... these were not clinically important in determining the safety profile."
In disbelief, Tramont's staff began inquiring how Smith's report got changed. An answer came back from the top.
"I wrote it," Tramont responded.
On the Net:
Documents gathered by AP for this story are available at: http://wid.ap.org/documents/nevirapine2.html
July 2005: Review Finds AIDS Agency 'Troubled'
National Institutes of Health: http://www.nih.gov
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See also Did AIDS drug put Africans at risk?
and these other documents from the AP about Nevirapine - page one - page three